Evidence map›Paper›PMID 26423134›Full record

ArticleNature communications2015

Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function.

Job de Lange, Atiq Faramarz, Anneke B Oostra, Renee X de Menezes, Ida H van der Meulen, Martin A Rooimans, Davy A Rockx, Ruud H Brakenhoff, Victor W van Beusechem, Randall W King and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 55 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Job de LangeDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Atiq FaramarzDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Anneke B OostraDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Renee X de MenezesDepartment of Epidemiology and Biostatistics, VU University Medical Center, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands.
Ida H van der MeulenDepartment of Medical Oncology, RNA Interference Functional Oncogenomics Laboratory, VU University Medical Center, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands.
Martin A RooimansDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Davy A RockxDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Ruud H BrakenhoffDepartment of Otolaryngology-Head and Neck Surgery, VU University Medical Center, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands.
Victor W van BeusechemDepartment of Medical Oncology, RNA Interference Functional Oncogenomics Laboratory, VU University Medical Center, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands.
Randall W KingDepartment of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Johan P de WinterDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Rob M F WolthuisDepartment of Clinical Genetics, section Oncogenetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Amsterdam UMC Location VUmc · NLHarvard University · US

Funding

Chemical Genetic Studies of MitosisR01GM066492 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KING, RANDALL W · 2002 to 2016
$4.7M
NIGMS NIH HHS R01 GM066492NIGMS NIH HHS R01 GM66492
6 · The paper itself

Abstract

Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in patient-derived cell lines reveals that WABS cells do not tolerate partial depletion of individual APC/C subunits or the spindle checkpoint inhibitor p31(comet). A combination of reduced cohesion and impaired APC/C function also leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines, and several cancer cell lines with cohesion defects, display a highly increased response to a new cell-permeable APC/C inhibitor, apcin, but not to the spindle poison paclitaxel. Synthetic lethality of APC/C inhibition and cohesion defects strictly depends on a functional mitotic spindle checkpoint as well as on intact microtubule pulling forces. This indicates that the underlying mechanism involves cohesion fatigue in response to mitotic delay, leading to spindle checkpoint re-activation and lethal mitotic arrest. Our results point to APC/C inhibitors as promising therapeutic agents targeting cohesion-defective cancers.

Indexed as

Anaphase-Promoting Complex-CyclosomeCell Cycle CheckpointsCell Cycle ProteinsCell LineChromosome SegregationHumansMitosisMorpholinesNocodazolePaclitaxelProtein Kinase InhibitorsPurinesRNA, Small InterferingSister Chromatid ExchangeTubulin Modulators2-(4-morpholinoanilino)-6-cyclohexylaminopurineAnaphase-Promoting Complex-CyclosomeCell Cycle ProteinsMorpholinesNocodazolePaclitaxelProtein Kinase InhibitorsPurinesRNA, Small InterferingTubulin Modulators

Identifiers

PMID26423134
PMCPMC4600715
OpenAlexW2173269264

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.